Quetiapine for Bipolar Disorder and Alcohol Dependence

The primary aim in the study is to determine if quetiapine treatment is associated with
greater reduction in alcohol use than placebo in outpatients with bipolar disorder and
alcohol dependence. We will also examine if quetiapine treatment is associated with greater
reduction in alcohol craving than placebo in outpatients with bipolar disorder and alcohol
dependence and if quetiapine treatment is associated with greater improvement in depressive
symptoms than placebo in outpatients with bipolar disorder and alcohol dependence.

Inclusion Criteria:

- Outpatients with a diagnosis of bipolar I or II disorder, depressed or mixed phase on
the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental
Disorders (SCID) and confirmed by interview with PI or co-I.

- Current diagnosis of alcohol dependence.

- Alcohol use (by self-report) of at least 15 drinks in the 7 days prior to baseline.

- Currently taking a mood stabilizer defined as lithium, divalproex/valproic acid,
oxcarbazepine, or lamotrigine at a stable dose for > 14 days.

- Men and women age 18-65 years old.

- English or Spanish speaking.

Exclusion Criteria:

- Bipolar disorders other than bipolar I or II (e.g., not otherwise specified or
cyclothymic disorders) based on the SCID and confirmed through clinical assessment by
PI or co-I.

- Baseline Young Mania Rating Scale (YMRS) score > 35 or Hamilton Depression Rating
Scale (HRSD) 17 score > 35.

- Current clinically significant psychotic features (hallucinations, delusions,
disorganized thought processes).

- Evidence of clinically significant alcohol withdrawal symptoms defined as a Clinical
Institute Withdrawal Assessment (CIWA-AR) score of > 8.

- History of hepatic cirrhosis or baseline AST or ALT > 3X upper limit of normal or
other clinically significant findings on physical or laboratory examination.

- Mental retardation or other severe cognitive impairment.

- Prison or jail inmates.

- Pregnant or nursing women or women of childbearing age who will not use oral
contraceptives, abstinence, or other acceptable methods of birth control during the
study.

- Antipsychotic therapy within 14 days prior to randomization.

- Current carbamazepine or benzodiazepine therapy.

- Current treatment with medications shown to reduce alcohol consumption (naltrexone,
acamprosate, disulfiram, or topiramate) in large randomized, controlled trials.

- Initiation of antidepressants or mood stabilizers or psychotherapy within past 2
weeks.

- High risk for suicide, defined as any suicide attempts in the past 3 months or current
suicidal ideation with plan and intent.

- Intensive outpatient treatment for substance abuse (AA, NA meetings, or other 12-step
programs or weekly psychotherapy that started at least 14 days prior to randomization
will be allowed).

- Current treatment with ketoconazole, itraconazole, erythromycin, or nefazodone.

- Severe or life-threatening medical condition (e.g., congestive heart failure, terminal
cancer) or laboratory or physical examination findings consistent with serious medical
illness (e.g., severe edema, atrial fibrillation, dangerously abnormal electrolytes).

- Diabetes mellitus by history or suspected from baseline blood sugar.

- History of cataracts or suspected cataracts on ophthalmic exam

- History of seizure disorder of any etiology; if a subject develops a seizure episode,
s/he will be discontinued from the study.